Drug Interaction Report

MONITOR: Coadministration of allopurinol with ampicillin or amoxicillin may increase the risk of skin rash and hypersensitivity. The mechanism of interaction is unknown, and it is unclear whether the condition of hyperuricemia or the actual exposure to allopurinol is responsible. In a retrospective study, 15 out of 67 patients (22%) who took ampicillin with allopurinol developed a skin rash, compared to 94 out of 1257 patients (7.5%) who took ampicillin without allopurinol. An updated study by the same group of investigators consisted of 252 patients who took ampicillin with allopurinol and 4434 who took ampicillin alone. The incidence of rash was 13.9% in the allopurinol group and 5.7% in the ampicillin-only group. Similar results were reported for amoxicillin. Specifically, 8 out of 36 patients (22%) treated concomitantly with allopurinol developed a rash, compared to 52 out of 887 patients (5.9%) on amoxicillin without allopurinol.

MANAGEMENT: Closer monitoring for the development of skin rash is recommended if ampicillin or amoxicillin are used concurrently with allopurinol. Some authorities suggest using an alternative to ampicillin or amoxicillin in patients receiving allopurinol when possible. Patients should be advised to promptly report any signs of skin hypersensitivity, including rash, pruritus, fever, or chills.

ADJUST DOSING INTERVAL: The tolerability of allopurinol may be improved by giving it after a meal. Additionally, when the dose is greater than 300 mg, dividing the total daily dose into smaller doses administered more often may be appropriate to help minimize gastrointestinal irritation.

MONITOR: Concomitant use of allopurinol with central nervous system (CNS) depressants, including alcohol, may potentiate adverse effects such as somnolence and sedation.

MANAGEMENT: To improve tolerability, some manufacturers suggest administering allopurinol after a meal. Additionally, if the daily dose is greater than 300 mg, administering allopurinol in divided doses may help reduce gastrointestinal intolerance. Patients should also be counseled to avoid or limit consumption of alcohol and to avoid activities requiring mental alertness such as driving or operating hazardous machinery until they know how the medication affects them.